Prostate cancer is the fifth leading cause of cancer death in men, responsible for over 375,000 deaths in 2020. Novel therapeutic strategies are needed to improve outcomes. Cannabinoids, chemical components of the cannabis plant, are a possible solution. Preclinical evidence demonstrates that cannabinoids can modulate several cancer hallmarks of many tumor types. However, the therapeutic potential of cannabinoids in prostate cancer has not yet been fully explored. The aim of this study was to investigate the antiproliferative and anti-invasive properties of cannabidiol (CBD) in prostate cancer cells in vitro. CBD inhibited cell viability and proliferation, accompanied by reduced expression of key cell cycle proteins, specifically cyclin D3 and cyclin-dependent kinases CDK2, CDK4, and CDK1, and inhibition of AKT phosphorylation. The effects of CBD on cell viability were not blocked by cannabinoid receptor antagonists, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, or an agonist of the G-protein-coupled receptor GPR55, suggesting that CBD acts independently of these targets in prostate cancer cells. Furthermore, CBD reduced the invasiveness of highly metastatic PC-3 cells and increased protein expression of E-cadherin. The ability of CBD to inhibit prostate cancer cell proliferation and invasiveness suggests that CBD may have potential as a future chemotherapeutic agent.
I say why not add it to ones protocol. My thoughts are if it can't hurt and may help then why not. Quality CBD oils are pricey, so If you can add it to without sacrificing other proven alt treatments then sure worth looking into. Everyone claims to have the best CBD so it's a real dive .
The metabolism of cannabis depends on the route of consumption. After oral consumption, THC travels to the liver where most of it is eliminated or metabolized. THC is metabolized into other molecules by CYP2C and CYP3A in the liver. These enzymes turn THC into 11-OH-THC, which is also psychoactive, and then into 11-COOH-THC, which is not psychoactive.24 More than 65% of cannabis is excreted in the feces and approximately 20% is excreted in urine.25 Most of the cannabis (80% to 90%) is excreted within 5 days as hydroxylated and carboxylated metabolites.26 Among the major metabolites, THC metabolite 11-COOH-THC is the primary glucuronide conjugate in urine, whereas THC metabolite 11-OH-THC is the predominant form in feces.27,28 The remaining THC and both its metabolites reach the heart and then enter the circulation. THC and 11-OH-THC reach the brain simultaneously. The bioavailability of ingested THC is only between 4% and 12%. THC is highly lipid soluble. It is rapidly taken up by fat tissue where it accumulates. From these fat deposits, THC is slowly released back into the bloodstream.29
After inhalation, THC and its metabolites enter the bloodstream quickly through the lung, with the peak achieved within 6 to 10 minutes after inhalation.30 Across all users, light and heavy, the bioavailability for inhaled THC is between 10% and 35%.30,31
In general, inhalation produces a stronger psychoactive effect than ingestion. After inhalation, THC concentrations are higher in the brain than in the blood.32 The plasma half-life of THC is approximately 1 to 3 days in occasional users and 5 to 13 days in chronic users.33
CBD is another chemical of cannabis. CBD enters the body similarly to THC. The pharmacokinetics of CBD is complex and the bioavailability of oral CBD is low across species.34-37 In general, the most abundant metabolites of CBD are hydroxylated 7-COOH derivatives that are excreted either intact or as glucuronide conjugates.38 CBD can either enhance or inhibit activation of its binding site targets. CBD blocks activation of the equilibrative nucleoside transporter (GPR55) and the TRP cation channel subfamily (glycine receptors, TRPM8), among others, and enhances activity of the serotonin 1A receptor, glycine receptors a1 and a3, and TRPA1.18
The route of administration affects the pharmacokinetics of CBD. Bioavailability via inhalation is 11% to 45% (mean 31%), whereas oral bioavailability of CBD is approximately 6% in humans. CBD has high lipophilicity. It rapidly distributes in the brain, adipose tissue, and other organs.18,35 CBD has low water solubility and absorption leads to variable pharmacokinetics if CBD is given in capsules. CBD given in oil products and by oral-mucosal/sublingual delivery through sprays or lozenges has less variability. The half-life of CBD is estimated at 18 to 32 hours.18,39
There are studies indicating that THC and CBD act on cytochrome P450 isoenzymes to affect the metabolism of various drugs. THC is a CYP1A2 inducer that may lead to reduced drug concentration via increased metabolism and consequently decreased drug effect. In contrast, CBD inhibits CYP3A4 and CYP2D6 and may lead to reduced drug concentration via enhanced metabolism, which thus exaggerates the drug’s effects and may result in substantial adverse reactions.40,41 In addition, drugs that are CYP3A4 inducers have been reported to reduce THC and CBD levels, whereas drugs that are CYP3A4 and CYP2C9 inhibitors increase THC and CBD levels.41,42"
I really appreciate this info. I've been considering a switch from Lupron to Orgovyx, but Orgovyx has over 300 negative drug interactions, including a listing for a significant one with CBD. I've been leaning hard on cannabis at bedtime to help sleep, reduce body pain in joints and muscles, significantly fewer times waking to pee, and anxiety.
My preferred method of administration is using a dry herb vape, a Davinci IQ2, which heats the ground flower to release the cannabinoids and terpenes with no combustion. About a decade ago I also did what's commonly referred to as the Rick Simpson protocol, taking a gram per day of concentrated cannabis oil; 1/3rd gram in an empty capsule every 8 hours. That was the first time I ever used cannabis, even having grown up as a teen in the '70s with ample opportunities. Shortly after I finished that 60 day protocol I visited an oncologist and my PSA was the lowest it had ever been measured, at <0.10. At the time, I was about 2 months overdue for my 6 month Lupron injection. I wish that lab could have measured lower. I'd like to do that protocol again sometime in the future.
I can't discuss cannabis with my current oncologist. From a casual discussion at the end of an appointment a few years ago I made a cursory mention of the upcoming vote to legalize medical cannabis in my current state, and he made his opinion very clear. So I do my own research on the topic and that's been sufficient until now, but diving into the interaction of liver enzymes and such extends beyond my level of understanding. I feel reasonably confident that I could take Orgovyx in the morning and use cannabis flower at bedtime without a problem.
My question is to first, confirm that assumption, and also to help understand what level of CBD would be a concern. I'm not using a CBD extract, only raw flower with tiny amounts of CBD, and if I would do that protocol again with cannabis oil it would be made from bud with only trace amounts of CBD. I know it's generally recommended to use a higher level of CBD with prostate cancer, but since I had good results with high-THC oil in the past, I'd probably do that same thing again.
I've been on Orgovyx for two years now. I generally vaporize cannabis flower using an HedrbalAire vaporizer a half dozen or so times daily. I also take a 50mg CBD capsule in the evening a couple hours before bedtime, and have been using CBD/cannabinoid suppositories since diagnosis in 2018 at bedtime too. My numbers are good and I haven't noticed any interactions or side effects with other meds. It's good to hear the RSO oil had a good effect for you. I don't live in a legal state so its hard to access here. I was born with glaucoma and stumbled on cannabis as a treatment on Oct. 3, 1972 after an exam revealed my pressures were normal that day. So I've been a medical cannabis patient for 51 years so far.
That's great to hear. Like I said, my biggest concern would be if/when I attempt that high-dose protocol again. I was able to spend several months in a legal state and an 'angel' donated enough oil to me for the entire protocol. He grows and processes his own oil. Eventually I had to return to my home state and lost legal access. Now it's legal here and my goal is to grow enough to make my own oil.
My oncologist hasn't prescribed Orgovyx, I was told it was because of the cost. I don't know whether or not it's a new thing, but they now have a patient assistance program that would make it feasible for me if I want to make the switch. I like the sounds of the reports I'm seeing of lower side effects, including potential for cardiac issues. My heart's not a problem for me currently, but I've been on Lupron 13 years and might be pushing my luck. My next shot is due in November and at the moment I'm thinking I might still get at least one more Lupron injection while I dig into this some more. I have heard that it takes a fair bit of CBD before you have to worry about that interaction, but there's practically no info out there to go by.
I asked about this in a FB cannabis healing group and received this in the comments. I can't vouch for this much one way or the other, except that it came from the primary guy offering advice in the group:
"Cbd has the ability to hinder the cyp450 liver enzymes family which is responsible for the Metabolization of about 86% of meds out there... and this one you are wanting to switch to is metabolized by the following 2 CYP3A & CYP2C8."
I take it around 5pm along with my daily dose of warfarin. I have an On-X carbon fiber aortic valve replacement from 2013 and that is the only blood thinner approved for use with it. Being on the warfarin also adds new wrinkles as it's a Vit K blocker.
So you only have a few hours between your Orgovyx and CBD, with no problems? That's great! And you're on a relatively high dose of CBD compared to anything I'm considering. For that matter though, considering that everyone's different, what signs do you think a person would see if they did experience an interaction?
I had virtually same experience on rso 60 gr. protocol... I now take a small piece of my homemade THC laden fudge made with rso each night before bed... Very potent...I sleep like a rock straight through, no aftereffects in a m. and I trust it's helping cancer to some degree too... Definitely medicine...
What form of cannabis did you add to your fudge? Decarbed flower, oil, or something else? I have some AVB (after-vaped bud) I water cured to get rid of the burnt taste that still has a little potency I could add to something like that.
I use 3oz of a very high indica strain trim like White Widow and make my own RSO through isopropyl alcohol extraction. The trim I use is as potent as flower. After cook-down I'm left with about 10 grams (ml) of RSO which I load into 1 ml oral syringes. Then I melt down a 20oz bag of GHIRARDELLI 60% Cacao bittersweet chocolate chips and add a 14oz can of Eagle condensed milk while chocolate is still hot. Then I squirt 7 syringes of the RSO into the mix and thoroughly mix it.
The condensed milk causes the chocolate to firm up quickly (becoming fudge) and then I cut and weigh it out into 2 to 3 gram pieces, one per night... I keep them refrigerated in sealed baggies... lasts for months... I should also mention that in addition to sleeping all night through, a 2 -3 gram piece renders me higher than a hawk's nest.👍
Sorry I'm slow responding here. How many pieces of fudge do you get out of a batch? And when you say you use 7 syringes, you mean 1 gram syringes, correct? Just trying to get a better idea of your daily dose.
BTW, have you ever considered using grain alcohol such as 190 proof Everclear? I know people who make their own oil and they all greatly prefer a food grade solvent and won't use isopropyl alcohol.
Yes, I put 7 one gram syringes of oil in the mix. I mix the oil, condensed milk and the melted chocolate very thoroughly. It soon begins to set up to where I can pick up the whole mixture blob out of the bowl by hand and further mix it by kneading. I use nitrile gloves because if not, the handling of the giant fudge ball gives immediate, major psychoactive effects via transdermal through hands.
The whole ball of fudge weighs in at just under 30 oz. I then cut and divide that into 6 equal baseball sized balls (approx 5 oz each), wrap them in Saran wrap and refrigerate.
Each night before bed I cut off a piece and weigh out a 2 to 3 gram piece and consume. (above I mistakenly stated I consume a "2oz" piece. I meant "gram", now corrected). It's delicious and very effective.
I used Everclear a few times for the solvent but I saw no difference in end product. Everclear is much more expensive than 91% isopropyl. As long as you thoroughly purge the oil to ensure all alcohol has completely evaporated, it's fine. Rick Simpson uses/used 91% iso...
All the fats in your fudge would likely really ramp up the effect of the THC. I know when I was doing a gram per day, my tolerance was fairly decent until I started adding oil with each dose. Man, what a difference. And if I take a dose now right after something like a pizza...wow.
Yes, I know Everclear is more expensive. Do you have a setup to capture it as it evaporates, like a still?
From my calculations, your batch has a bit of irony built in. 30 ounces = about 840 grams. And at 2 grams per dose, that means you have 420 doses. LOL!
Your calculations are really accurate. I actually made a batch of oil and fudge yesterday, first time in about a year which is why I keep only one ball in refrigerator and the others in freezer, taking them out as I need them.... while keeping my stash of trim in sealed mason jars....
No, I have no reclamation apparatus for the alcohol...its really good idea, not just for savings but for environment too I guess... I may look into that further but I cook off the oil/alcohol in a large Teflon frying pan on a small electric hotplate out on our deck. The fumes are extremely volatile so I fear even the start up of the refrigerator might spark off an explosion if done indoors... I wonder what neighbors might think if they see me out on the deck with what would look like a moonshine still.😄😄
Also, forgot to mention that I don't weigh out precisely 2 grams. It's approximate, only occasionally using scale...and on weekends I enjoy a bit more, like around a double dose for recreational use, going to bed in a nice heightened state of euphoria... like right now, Friday night...😄 So I believe your calculations are spot on bro!..👍
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